4-Bromobenzyl-5-MeO-T
I am a little bit prejudiced with the N-benzyl-compounds. I remember a paper from Glennon et al. :
Influence of Amine Substituents on 5-HT2A versus 5-HT2C Binding of Phenylalkyl- and Indolylalkylamines. Glennon, Richard A.; Dukat, Malgorzata; El-Bermawy, Mohamed; Law, Ho; De Los Angeles, Joseph; Teitler, Milt; King, Allison; Herrick-Davis, Katharine. Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA. Journal of Medicinal Chemistry (1994), 37(13), 1929-35.
Abstract
The effect of different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of phenylalkylamine and indolylalkylamine derivs. I and II [R = H, R1 Me, Et, (CH2)3Ph, (CH2)4Ph, CH2C6H4R2, R2 = H, F, Cl, Br, iodo, Me, NH2, NO2, OMe; R = R1 = Me; NRR1 = piperidino]. In general, amine substitution decreases receptor affinity;however, N-(4-bromobenzyl) substitution results in compds. that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with >100-fold selectivity. Although parallel structural modifications in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.
His most promising compound seemed to be the N-(4-bromobenzyl).5-MeO-T.
I know honorable people who made it and tested it up to 3 mg orally with no effect. The binding data would indicate that this compound should be active at this level. –So the oral availibility might be responsible for that. –Or any other thing.